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Novel Therapeutic Strategies for Metastatic TNBC

Danielle Bucco
Published: Friday, Jul 21, 2017

Joyce O’Shaughnessy, MD,
Joyce O’Shaughnessy, MD,
An evolving understanding of the biology and heterogeneity of triple-negative breast cancer (TNBC) is helping to refine existing approaches to treating patients and is yielding intriguing insights into current and novel therapies, according to Joyce A. O’Shaughnessy, MD.

O’Shaughnessy provided an analysis of emerging therapeutic strategies for TNBC during a presentation at the 16th Annual International Congress on the Future of Breast Cancer® West that Physicians’ Education Resource (PER®) hosted July 14-15 in San Diego, California. She is the co-chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center in Dallas and for The US Oncology Network and she served as program co-chair for the conference.

In her presentation, O’Shaughnessy covered a broad range of data concerning multiple new and approved drugs. Here are some of the key areas she discussed:

Molecular Subtyping

So far, the clinical utility of molecular subtyping approaches in TBNC has not been established but it is shaping up to be valuable knowledge, with some therapeutic signals that correlate with subtypes, O’Shaughnessy said.

There have been several studies delineating intrinsic subtypes in TNBC, O’Shaughnessy said, notably a 2016 analysis that refined TNBC molecular subtypes into 4 tumor-specific categories: basal-like 1, basal-like 2, mesenchymal, and luminal androgen receptor.1 Lehmann et al retrospectively examined pretreatment tissue samples from 300 patients with TNBC and found significant differences among the subtypes in pathological complete responses to neoadjuvant chemotherapy.

“This subtyping is more to help us as clinicians begin to think about what to do with this very heterogeneous disease and why clinical trials are evolving as they are,” said O’Shaughnessy.

Chemotherapy Doublets

Although research findings have not been specifically matched with a molecular subtype in the tnAcity study, O’Shaughnessy pointed to the results of the phase II trial as setting the stage for a new first-line chemotherapy doublet for patients with TNBC.

In the study, 191 patients were randomized to receive nab-paclitaxel (Abraxane) plus carboplatin (n = 64), nab-paclitaxel plus gemcitabine (n = 61), or gemcitabine plus carboplatin (n = 66. The overall response rate (ORR) was 72% with the nab-paclitaxel/carboplatin regimen compared with 39% and 44%, respectively, for the gemcitabine-containing regimens.2

The combination of nab-paclitaxel plus carboplatin proved superior in median progression-free survival (PFS): 7.4 months compared with 5.4 months for nab-paclitaxel/gemcitabine (HR, 0.60; CI 95%, 0.39-0.93; P = .02) and 6.0 months for gemcitabine/carboplatin (HR, 0.61; 95% CI, 0.39-0.94; P = .03). The median overall survival was 16.4 months with nab-paclitaxel/carboplatin versus 12.1 months with nab-paclitaxel plus gemcitabine (HR, 0.66; CI 95%, 0.42-1.04; P = .07) and 12.6 months with gemcitabine plus carboplatin HR, 0.74; CI 95%, 0.48-1.16; P = .17).

Regarding the toxicity profile, O’Shaughnessy noted that the nab-paclitaxel regimens were more favorable from a myelosuppression standpoint.

O’Shaughnessy said gemcitabine plus carboplatin has been historically used as the doublet of choice for this patient population. However, based on the tnAcity findings, “it would not be unreasonable to consider a nab-paclitaxel and carboplatin combination as an option,” she said.

PARP Inhibitors

The strategy of using a PARP inhibitor to target the DNA repair mechanism proved effective in the phase III OlympiAD study in which olaparib (Lynparza) provided a statistically significant PFS benefit for patients with TNBC. 3 The safety profile of olaparib was consistent with prior studies.

In this study, 302 patients were randomized, with 205 patients receiving olaparib and 91 receiving the single-agent chemotherapy of physician’s choice, such as capecitabine (Xeloda), eribulin (Halaven), or vinorelbine (Navelbine). Patients on the olarparib arm received 300 mg twice a day until objective disease progression or unmanageable toxicity. PFS was the primary endpoint.

The study enrolled patients with HER2-negative metastatic breast cancer including participants with estrogen receptor– and/or progesterone receptor–positive disease or TNBC. Patients were required to have a germline mutation in BRCA1/2 genes, which are important components of a key DNA repair pathway.


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Online CME Activities
TitleExpiration DateCME Credits
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
34th Annual Miami Breast Cancer Conference® Clinical Case Vignette Series™May 25, 20182.0
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